ALS-associated KIF5A mutations abolish autoinhibition resulting in a toxic gain of function.

Understanding the pathogenic mechanisms of disease mutations is critical to advancing treatments. ALS-associated mutations in the gene encoding the microtubule motor KIF5A result in skipping of exon 27 (KIF5AΔExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore, mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis.

Garments and Footwear for Chronic Pain.

In most human societies, wearing clothing and shoes, particularly in public settings, is commonplace and may even be legally required. Consequently, there is an abundance of clothing and footwear options for individuals of different ages, genders, body shapes and catering to different needs such as workwear and active-wear. However, many of the available options may not be viable for the millions and pain sufferers worldwide, indicating a need for adaptive apparel for the pain patient. In this perspective manuscript, we focus on the availability and efficacy of clothing designed to prevent pain in the general population as well as reduce or treat pain in pain patients. Furthermore, we put forth some considerations for the construction of adaptive garments. Such efforts and needed and could significantly improve well-being and quality of life in the pain patient.

Babesiosis caused by Babesia vogeli in dogs from Uberlândia State of Minas Gerais, Brazil.

Babesia is tick-transmitted protozoan parasites that infect mammalian hosts and have a major impact on farm and pet health-associated costs worldwide. This study aimed to test the prevalence of Babesia spp. infection in a small cohort of dogs at a veterinary hospital and to perform molecular characterization of the Babesia species causing the infection. For the PCR assay, 5 mL of blood was collected by venipuncture of the cephalic or radial veins in 300 dogs of different ages, sex, and breeds, which were presented to the veterinary hospital of the Federal University of Uberlândia between March 2015 and April 2016. In addition, a drop of blood was collected from the marginal blood vessels of the ear of dogs included in this study. Ninety-two (30.67%) were positive for Babesia spp., as determined by microscopic observation of the blood smear, revealing the presence of intra-erythrocyte merozoites. For molecular characterization by PCR, 17 samples were chosen from dogs who were tested positive for Babesia spp. by blood smears. Among them, B. vogeli was found to infect all 17 dogs, as determined by 99-100% sequence identity (closest GenBank match KT246307) using primers PIRO A/PIRO B. Our results indicate that the species observed in these dogs was B. vogeli.

Caracterización del estado clínico audiológico de los trabajadores de una empresa minera en Nicaragua, Noviembre 2015 / Characterization of the clinical audiological status of the workers of a mining company in Nicaragua, November 2015

Estudio descriptivo de corte transversal el cual constó de un universo y muestra que estuvo conformada por trabajadores un empresa minera (400 personas) que tenían indicada audiometría por realizar trabajos con exposición a ruido mayor o igual a 85 dBA durante el período de estudio, se trabajó con fuentes secundarias que fue creada a partir de una ficha audiológica. La Edad predominante 19 y 29 años (52.25%). Según sexo 384 (96%) son hombres y 16 (4%) son mujeres. Cargo predominante Mineros/ Perforista 134 (33.5 %). Utilizaban doble protección auditiva (Tapones y orejeras) 251 (62.75 %). El antecedente patológico personal que predomina es la Varicela 103 (25.75 %), seguido de Infecciones óticas 47 (11.75 %). El antecedente no patológico que predomina es el uso de hisopos con un 310 (77.5 %) seguido por frecuentar discotecas con 143 (35.75 %). De las audiometrías estudiadas se encontraron 316 (79 %) normales y 84 (21 %) alteradas. De las audiometrías alteradas 71 (17.75 %) son Hipoacusias comunes y 13 (3.25 %) son Hipoacusias de posible causa laboral. La gran mayoría del personal estudiado es joven, son hombres, tienen pocos años de laborar son mineros/ Perforistas. Utilizaban doble protección auditiva (Tapones y orejeras). Su antecedente patológico personal predominante es la Varicela seguido de infecciones óticas. El antecedente no patológico que predomina es el uso de hisopos seguido por el hábito de frecuentar discotecas. La mayoría de las otoscopias estaban normales, pero en las alteradas predomina el tapón de cerumen y el eritema en conductos auditivos. El principal síntoma ótico es el prurito. La minoría de las audiometrías estudiadas están alteradas y en mayor parte corresponden a Hipoacusias comunes en menor cantidad a Hipoacusias de posible causa laboral

Perioperative evaluation of tumescent anaesthesia technique in bitches submitted to unilateral mastectomy.

BACKGROUND: Tumescent anaesthesia (TA) is a widely used technique in oncologic surgeries necessitating large resection margins. This technique produces transoperative and postoperative analgesia, reduces surgical bleeding, and facilitates tissue divulsion. This prospective, randomised, blind study evaluated the use of TA in bitches submitted to mastectomy and compared the effect of TA with an intravenous fentanyl bolus. A 2.5-mcg/kg intravenous fentanyl bolus (n = 10) was compared with TA using 0.275% lidocaine (n = 10) in bitches submitted to unilateral mastectomy. Sedation was performed by intramuscular (IM) injection of 0.05 mg/kg of acepromazine combined with 2 mg/kg of meperidine. Anaesthesia was induced with 5 mg/kg of intravenous propofol and maintained with isoflurane/O2. Heart and respiratory rates; systolic, mean, and diastolic arterial blood pressures; central venous pressure; SpO2; ETCO2; inspired and expired isoflurane concentrations; and temperature were measured transoperatively. Visual analogue scales for sedation and pain and the Glasgow composite and Melbourne pain scales were used for postoperative assessment. The surgeon investigated the quality of the surgical approach, considering bleeding and resection ability, and the incidence of postoperative wound complications. RESULTS: The heart rate was lower and the end-tidal isoflurane concentration was higher in dogs treated with fentanyl than in dogs treated with TA. A fentanyl bolus was administered to 8 of 10 dogs treated with fentanyl and to none treated with TA. Intraoperative bleeding and the mammary gland excision time were lower in dogs treated with TA. The maximal mean and individual plasma lidocaine concentrations were 1426 ± 502 ng/ml and 2443 ng/ml at 90 minutes after infiltration, respectively. The Glasgow Composite Pain Scale scores were higher in dogs treated with fentanyl than in dogs treated with TA until 2 hours after extubation. CONCLUSIONS: Compared with intravenous fentanyl, TA in bitches: may be easily performed in non-inflamed, ulcerated, adhered mammary tumours; has an isoflurane-sparing effect; improves transoperative and immediate postoperative analgesia; is apparently safe for use in clinical conditions as evidenced by the fact that it did not produce any adverse signs or lidocaine plasma concentrations compatible with toxicity; does not modify the recovery time; and facilitates the surgical procedure without interfering with wound healing.

Synthesis and characterization of biomimetic nanogels for immunorecognition.

Biomimetic nanoparticles are promising materials for biomedical and biotechnological applications. Cationic poly(N-isopropylacrylamide) (PNIPAM) nanogels containing charged amine groups brought by addition of 2-aminoethylmethacrylate hydrochloride (AEMH) or N-(3-aminopropyl) methacrylamide hydrochloride (APMH) as co-monomers were prepared by surfactant-free precipitation polymerization. The influence of the relative amount and mode of addition of the co-monomer on both the size and the amine group density of the nanogel particles was studied. Two nanogels, one prepared using APMH (1%mol/mol NIPAM, in batch) and another with AEMH (2%mol/mol NIPAM, by shot addition) as co-monomers, were selected for the covalent coupling of a Protein L-mimic ligand to free amine groups on the particles. The ability of the synthesized biomimetic nanoparticles for recognizing and binding human IgG (hIgG) molecules was assessed and the selectivity toward immunoglobulin molecules evaluated.

Estado nutricional y su asociación con depresión y autoestima en una población de adultos / Nutritional status and its association with depression and self-esteem in a population of older adults in the state of Mexico / Estado nutricional e sua associação com depressão e auto-estima em uma população de idosos no estado do México

Antecedentes: La población de adultos mayores es uno de los grupos con mayor incremento en la población mundial, por lo que se considera de vital importancia la detección de los problemas nutricionales ya sea por déficit o exceso, dado por el propio proceso de envejecimiento se ha demostrado que durante esta etapa los cambios guardan relación con estados de depresión y autoestima baja; lo que influye de manera determinante para presentar estados de fragilidad. En estudios relacionados se demuestra la importancia de realizar evaluaciones del estado nutricional y su relación con diversos estados anímicos, es por ello que este estudio recobra gran importancia ya que si de manera anticipada se realizaran dichas evaluaciones los factores de riesgo se conocerían y sería posible determinar estrategias específicas e inclusive personalizadas para limitar este problema de salud; las cuales pueden desarrollar los profesionales de enfermería, mejorando así la calidad de vida de los adultos mayores. Objetivo: Determinar el estado nutricional y su asociación con depresión y autoestima en una población de adultos mayores del Estado de México. Método: Se llevó a cabo un estudio, observacional, pro lectivo, transversal y descriptivo. Se obtuvo una muestra de 157 adultos mayores de 60 años y más, en dos unidades médicas de atención ambulatoria, hospital para enfermos crónicos Tepexpan Dr. Gustavo Baz, en el municipio de Acolman y el hospital delas Américas del municipio de Ecatepec de Morelos ambas pertenecientes al Instituto de Salud del Estado de México en un periodo de Noviembre 2012 a Febrero del 2013, a los cuales se les aplicó a través de interrogatorio directo y los siguientes instrumentos: Escala de Depresión Geriátrica de Yesavage (o Geriatric Depression Scale, GDS) Escala de valoración de Autoestima (Rosenberg), Medidas antropométricas (peso, talla, IMC, CMB, ICC). Los resultados fueron analizados empleándose estadística: estadística descriptiva, frecuencias, porcentajes, valores promedio ± desviación estándar y como pruebas de comparación X

Background: The elderly population is one of the groups with the greatest increase in the world population, so it is considered vitally important to detect nutritional problems either due to deficit or excess, given by the aging process itself. demonstrated that during this stage the changes are related to states of depression and low self-esteem; which influences in a decisive way to present states of fragility. Related studies demonstrate the importance of evaluating nutritional status and its relationship with various moods, which is why this study is very important because if these evaluations were carried out in advance, the risk factors would be known and it would be possible to determine specific and even customized strategies to limit this health problem; which can be developed by nursing professionals, thus improving the quality of life of older adults. Objective: To determine the nutritional status and its association with depression and self-esteem in a population of older adults in the State of Mexico. Method: An observational, pro-lecture, cross-sectional and descriptive study was carried out. A sample of 157 adults over 60 years of age and older was obtained in two outpatient medical units, Tepexpan Dr. Gustavo Baz chronic patients hospital, in the municipality of Acolman and the Americas hospital in the municipality of Ecatepec de Morelos both belonging to the Health Institute of the State of Mexico in a period from November 2012 to February 2013, to which they were applied through direct interrogation and the following instruments: Yesavage Geriatric Depression Scale (or Geriatric Depression Scale, GDS) Self-esteem rating scale (Rosenberg), Anthropometric measurements (weight, height, BMI, CMB, ICC). The results were analyzed using statistics: descriptive statistics, frequencies, percentages, average values ​​± standard deviation and as comparison tests X

Antecedentes: A população idosa é um dos grupos com maior aumento na população mundial, por isso é considerado de vital importância a detecção de problemas nutricionais por déficit ou excesso, decorrentes do próprio processo de envelhecimento. demonstraram que nessa fase as alterações estão relacionadas a estados de depressão e baixa autoestima; que influencia de maneira decisiva para apresentar estados de fragilidade. Estudos relacionados demonstram a importância de avaliar o estado nutricional e sua relação com os vários humores, razão pela qual este estudo é muito importante, porque se essas avaliações fossem realizadas com antecedência, os fatores de risco seriam conhecidos e seria possível determinar estratégias específicas e até personalizadas para limitar esse problema de saúde; que pode ser desenvolvida pelos profissionais de enfermagem, melhorando a qualidade de vida dos idosos. Objetivo: Determinar o estado nutricional e sua associação com depressão e auto-estima em uma população de idosos do Estado do México. Método: Estudo observacional, pró-palestra, transversal e descritivo. Uma amostra de 157 adultos com mais de 60 anos de idade foi obtida em duas unidades médicas ambulatoriais, o hospital de pacientes crônicos Tepexpan Dr. Gustavo Baz, no município de Acolman e o hospital das Américas no município de Ecatepec de Morelos, ambos pertencentes ao Instituto de Saúde do Estado do México, no período de novembro de 2012 a fevereiro de 2013, ao qual foram aplicados por meio de interrogatório direto e pelos seguintes instrumentos: Escala de Depressão Geriátrica Yesavage (ou Escala de Depressão Geriátrica, GDS) Escala de avaliação da autoestima (Rosenberg), medidas antropométricas (peso, altura, IMC, CMB, ICC). Os resultados foram analisados ​​por meio de estatística: estatística descritiva, frequências, porcentagens, valores médios ± desvio padrão e, como testes de comparação X

Wintering area DDE source to migratory white-faced ibis revealed by satellite telemetry and prey sampling.

Locations of contaminant exposure for nesting migratory species are difficult to fully understand because of possible additional sources encountered during migration or on the wintering grounds. A portion of the migratory white-faced ibis (Plegadis chihi) nesting at Carson Lake, Nevada continues to be exposed to dichloro-diphenyldichloro-ethylene (DDE) with no change, which is unusual, observed in egg concentrations between 1985 and 2000. About 45-63% of the earliest nesting segment shows reduced reproductive success correlated with elevated egg concentrations of >4 microg/g wet weight (ww). Local prey (primarily earthworms) near nests contained little DDE so we tracked the migration and wintering movements of 20 adult males during 2000-2004 to determine the possible source. At various wintering sites, we found a correlation (r (2) = 0.518, P = 0.0125, N = 11) between DDE in earthworm composites and DDE in blood plasma of white-faced ibis wintering there, although the plasma was collected on their breeding grounds soon after arrival. The main source of DDE was wintering areas in the Mexicali Valley of Baja California Norte, Mexico, and probably the adjacent Imperial Valley, California, USA. This unusual continuing DDE problem for white-faced ibis is associated with: the long-term persistence in soil of DDE; the earthworms' ability to bioconcentrate DDE from soil; the proclivity of white-faced ibis to feed on earthworms in agricultural fields; the species's extreme sensitivity to DDE in their eggs; and perhaps its life history strategy of being a "capital breeder". We suggest surveying and sampling white-faced ibis eggs at nesting colonies, especially at Carson Lake, to monitor the continuing influence of DDE.

Experiencia con venlafaxina en Venezuela / Experience with venlafaxine in Venezuela

Se realizó un estudio abierto, no comparativo, multicéntrico, prospectivo en el cual fueron incluidos 171 pacientes con diagnóstico de depreción mayor (leve, moderada y severa), fue realizado por 39 psiquiatras en 10 ciudades de Venezuela. Los objetivos del estudio fueron determinar la eficacia, seguridad y tolerancia de la venlafaxina, una nueva droga antidepresiva en pacientes ambulatorios. La Sociedad Venezolana de Psiquiatría aprobó el protocolo del estudio. Los pacientes llenaban los criterios diagnósticos para depresión mayor de la DSM-III-R. La escala para evaluación de depresión de hamilton y la de impresión clínica global (ICG) fueron utilizadas para determinar la respuesta clínica de los pacientes a la medición. Los pacientes fueron distribuidos en diferentes grupos de dosis (37,5 - 75 mg, 100 - 150 mg y de 175 - 300 mg) de acuerdo a su puntuación al inicio del estudio en la escala de hamilton. Los pacientes fueron evaluados durante 6 semanas. Un total de 118 pacientes completaron el estudio (69 por ciento) de los 118 casos, 50 tenían depresión leve, 39 moderada y 29 severa. Después de 7 días de tratamiento con venlafaxina se apreció una mejoría estadísticamente significativa en pacientes con depresión leve a moderada en la escala ICG como se observa a continuación: en dosis de 37,5 a 75 mg hubo una mejoría marcada a los 7 días en el 36,8 por ciento, después de 14 días en el 76,3, después de 28 días en el 91,1 por ciento y a los 42 días en el 94,7 por ciento. En el grupo de dosis de 100 a 150 mg hubo una mejoría marcada a los 7 días del 37,5 por ciento, en el día 14 del 53,3 por ciento, en el día 28, 78,1 por ciento y al día 42 de 89,3 por ciento. Todos estos resultados fueron estadísticamente significativos. En el grupo de dosis de 150 a 300 mg a los 7 días fue de 0 por ciento, al día 14 de 33,3 por ciento, al día 28 de 55,6 por ciento y al día 42 de 41,4 por ciento. Todos estos resultados fueron estadísticamente significativos. De acuerdo a la esc...